1. Field of the Invention
The present invention relates to a method and apparatus for acquiring well-resolved, high-definition images or high resolution spectral data even when dealing with heterogeneous media. And more particularly, to a method and apparatus for acquiring uni- or multidimensional nuclear magnetic resonance images or spectra within a single or multiple scans, even when the sample is subject to inhomogeneous magnetic fields, or to other kinds of spatial or chemical heterogeneities. The present invention also relates to a variety of methods employing the principles of these methods or techniques.
2. Prior Art
“Ultrafast” nuclear magnetic resonance imaging (MRI) methods can afford multidimensional profiles of a sample in a non-invasive fashion, and within a fraction of a second [1, 2].1 Pivotal to this development was Mansfield's introduction of the k-space concept [3], leading eventually to echo-planar-imaging (EPI) and to subsequent ultrafast propositions [4-6]. Like its Jeener-Ernst nD nuclear magnetic resonance (NMR) spectroscopy counterpart [7, 8] EPI retrieves multidimensional information by monitoring the spins' behavior as a function of time, rather than by monitoring their response at a predefined set of irradiation frequencies. A subsequent Fourier transform (FT) of the free induction decay signals (FIDs) is thus needed to extract the relative contributions of the intervening Bohr precession frequencies to the spins' spectrum. Unlike what is done in conventional 2D NMR spectroscopy, where the two frequencies to be correlated occupy separate portions of the experiment, 2D EPI alternates the relative contributions of the frequencies defining the spins' evolution in such fashion so as to deliver the complete 2D time-domain interferogram following a single excitation of the spins. This “k-walk” principle can be carried out by switching the intervening gradients or by modulating them in a concurrent fashion, leading to a variety of related ultrafast acquisition modes [1, 4, 9-12]. These have eventually become one of the cornerstones of modern MRI and underlie several contemporary fields in medical research, including functional organ studies, the imaging of rapidly changing and/or pulsating systems, real-time interventional imaging, and rapid angiographic characterizations [1, 2]. 1 Abbreviations: EPI—echo planar imaging; FID—free induction decay; FOV—field of view; FT—Fourier transformation; MRI—magnetic resonance imaging; nD—arbitrary one or multi-dimensional experiment; NMR—nuclear magnetic resonance.
In an effort to emulate EPI's advantages, it has been recently proposed to use an alternative nD NMR acquisition scheme capable of affording arbitrarily high-dimensional data sets within a single scan [13-16]. By contrast to the imaging-derived k-scanning methodologies, however, the new nD single-scan protocol is applicable within a purely spectroscopic scenario or within an imaging-oriented one [16, 17]. Underlying this “ultrafast NMR” approach is the sequential, single-shot encoding of the NMR interactions one is attempting to measure, along an ancillary inhomogeneous frequency domain. This is most often introduced by the application of an external magnetic field gradient, which endows spins located at different positions with individually addressable frequencies. When applied in conjunction with a frequency-incremented excitation or inversion of the spins, such gradients lead to the possibility of “spatial encoding” the NMR interactions to be measured. In other words they allow one to encode the spin interactions Ω1 with a phase φ(r)≈CΩ1(r−r0), rather than with the usual temporal encoding φ(t)≈Ω1·t. Patterns encoded in such fashion can be subject to a mixing process, and subsequently read out with the aid of a seconds acquisition gradient, revealing their initial evolution frequencies according to echo positions arising at k=−CΩ1. Furthermore, subjecting this acquisition gradient to multiple oscillations allows one to monitor the actions of a second, direct-domain set of NMR Hamiltonians. This multiple-readout feature opens up the possibility to collect multidimensional NMR correlations within a single scan, irrespective of the details of the NMR experiment under question. At the moment spatial encoding offers the sole approach to the completion of generic nD NMR spectroscopic acquisitions within a single scan; at the same time and within a purely imaging framework, it offers an alternative to ultrafast MRI protocols based on 2D FT, such as EPI.
In addition to enabling the acquisition of multidimensional NMR/MRI data sets within a single scan, the position-dependent encoding of the interactions just described opens up another possibility: the acquisition of high-resolution NMR spectra from bulk samples, even when these are subject to local or global inhomogeneities of the magnetic field. Indeed as we have illustrated in a purely spectroscopic scenario [18, 19] the spatial encoding underlying ultrafast NMR can also be exploited in order to correct, at the time of the spatially-dependent spin excitation, for the effects that field distortions will have at a later time when the signal acquisition will take place. Related compensation principles have also been demonstrated along direct acquisition domains with the introduction of so-called “shim pulses” [20]. These procedures do not entail a betterment of the fields but rather radiofrequency (RF) manipulations, which can address either longitudinal (B0) or transverse (B1) field distortions by manipulations of the phase and/or amplitudes of the pulses.
Nuclear Magnetic Resonance spectroscopy can deliver unique chemical insight in a non-invasive fashion [33]. To do so, however, it demands an extremely high homogeneity from the external magnetic field B0 where the experiment takes place. Field inhomogeneities ΔB0(r)=γΩinh(r) need to be reduced until made small vis-à-vis the smallest internal shifts or couplings to be measured, when considered over the full sample volume. This translates in demanding that field perfections be better than 1 part in 108 over sample volumes on the order of 1 cm3; a significant challenge requiring serious investments in both the size of the main magnet and the number of auxiliary shimming coils to be used [34]. Moreover instances arise where even the most extensive efforts cannot deliver the required field homogeneity; for example when dealing with samples subject to substantial internal susceptibility distortions, or when dealing with sudden changes in the nature of the medium being examined. All of these are common scenarios in a variety of in vivo NMR spectroscopy experiments [35], where the achievement of high resolution is further aggravated by the relatively low length-to-width ratio of the typical animal or clinical magnet, and by the advent of higher magnetic field strengths requiring an increasing number of higher-order shims to achieve the needed field corrections. An ultimate example of these complications is found in ex situ NMR experiments, whose goal is to obtain high resolution spectroscopic information from objects operating on the basis of single-sided magnets [36].
In an effort to overcome these complications, a number of alternatives have been proposed for collecting high resolution chemical information in the presence of field distortions. One of the first strategies to be demonstrated involved the use of two-dimensional (2D) NMR experiments, where high resolution was achieved by correlating the effects of arbitrary field inhomogeneities at a particular chemical site with identical effects affecting neighboring sites in the spin system [37, 38]. While the reliance of these experiments on relatively weak multi-spin correlations did not endow them with the highest of sensitivities, they showed an advantage over competing proposals in that they dealt equally well with 1D, 2D or 3D Ωinh(r) distributions. These 2D correlations have therefore served as basis for a variety of high-resolution NMR experiments in inhomogeneous fields [39, 40]. Another compensation approach to remove field inhomogeneities proposed the use of custom-built radiofrequency (RF) coils, whose B1 distortions matched spatially those of the B0 field [41, 42]. Recently a different route for exploiting RF fields to compensate for ΔB0 inhomogeneities possessing a priori arbitrary spatial dependencies has been described; this involved the combined application of a field gradient spreading out the spins resonance frequencies according to their spatial positions, in conjunction with a suitable train of excitation or refocusing RF pulses whose phases compensate for the cumulative effects of the inhomogeneities [18, 19]. Worth mentioning in connection to this approach yet in a fast-imaging context is also the use of tailored-RF excitation pulses applied in combination with a slice-selection gradient, in order to compensate for susceptibility distortions arising in echo-planar-imaging acquisitions at the instant of the main gradient-echo formation [44, 32].